Investigating the effect of increased dopamine signaling on cerebral blood flow in Major Depressive Disorder: a double-blind randomized placebo-controlled study.

Overview

1. MSB Medical School Berlin,Berlin, Germany
2. Department of Education and Psychology, Freie Universität Berlin,Berlin, Germany
3. Charité Research Organisation GmbH,Berlin, Germany
4. SBGneuro Ltd, Littlemore,Oxford, UK
5. Donders Institute, Centre for Medical Neuroscience, Radboud University Medical Centre,Nijmegen, Netherlands
6. Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, University of Oxford,Oxford, UK
7. Clinical Development and Operations, Boehringer Ingelheim Pharma GmbH & Co. KG,Biberach an der Riss, Germany
8. Medicine Therapeutic Area CNS-Retinopathies-Emerging Areas, Boehringer Ingelheim International GmbH,Biberach an der Riss, Germany
9. Private Consultant, Lübeck, Germany

Abstract

Anhedonia, a core symptom of major depressive disorder (MDD), is linked to dysfunction in reward-related brain regions and impaired dopamine (DA) signaling. This study used arterial spin labeling (ASL) to investigate the effects of a single low dose of amisulpride, a selective DA antagonist, on cerebral blood flow (CBF) in MDD patients and healthy volunteers (HVs). In a double-blind, placebo-controlled, randomized, parallel-group design, participants received either 100 mg amisulpride or placebo. N = 111 participants (MDD: n = 57; HV: n = 54) were included in the final analysis and group differences were assessed in core regions of the reward network, particularly the ventral striatum. Individual CBF values were analyzed in relation to self-reported anhedonia and depression severity. Amisulpride was associated with higher perfusion in the ventral striatum compared to placebo in both HVs and MDD patients, consistent with enhanced dopaminergic activity in this region. No significant CBF changes were observed in other areas of the reward network. Ventral striatal perfusion was significantly associated with self-reported anhedonia. Exploratory whole-brain analyses revealed higher CBF in the right frontal operculum in MDD patients compared to HVs under placebo, but not under amisulpride. In the placebo group, both anhedonia and depression severity were associated with CBF in the right frontal operculum; these associations were absent following amisulpride administration. In conclusion, we provide initial evidence of region-specific effects of amisulpride administration on CBF that are consistent with modulation of dopaminergic signaling. Increased perfusion in the ventral striatum suggests a potential dopaminergic mechanism relevant to anhedonia. These findings underscore the ventral striatum’s role in reward processing and support its involvement in the pathophysiology of anhedonia across clinical and non-clinical populations.

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The individual de-identified participant data and the statistical code can be accessed upon reasonable request from the corresponding author.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 2 keywords, 17 MeSH terms, 1 funder, 80 references.

Cite

This paper

Gärtner, M., Meiering, M. S., Weigner, D., Hempel, M., Gruzman, R., Carstens, L., Keicher, C., Mennes, M., Beckmann, C. F., Luippold, G., Süssmuth, S. D., Popp, M., Wunder, A., & Grimm, S. (2026). Investigating the effect of increased dopamine signaling on cerebral blood flow in Major Depressive Disorder: a double-blind randomized placebo-controlled study. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 51(10), 1808-1815. https://doi.org/10.1038/s41386-026-02471-6

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